Depression

in Parkinson's disease
 Introduction

 Parkinson's disease (PD)  multisystem disorder with motor and nonmotor

symptoms (NMS).
 NMS  cognitive impairment, apathy, depression or anxiety, sleep disorder,
olfactory loss, and dysautonomia
 Depression is the most common neuropsychiatric symptom in PD patients.
 Our previous study revealed that PD patients with premotor symptoms (including
depression, rapid eye movement sleep behaviour disorder, and constipation) 
increased mortality and morbidity (dementia and aspiration pneumonia) compared
to PD patients without premotor symptoms
 the present study  evaluated the association between the onset of depression
from PD diagnosis and the outcomes of PD
Methods
 Patients were defined as newly-diagnosed PD  between January 2001 and
December 2008.
Included  patients whose diagnostic code of PD was made more than three times
in outpatient services, or more than once during hospitalization
Excluded 
 patients who were exposed to medicines with a high risk of drug-induced
parkinsonism more than three times within three months before the diagnosis of
PD.
 patients with the disease, potentially causing secondary or atypical Parkinsonism
 Participants who had never taken any anti-parkinsonian medicine after diagnosis
of PD were also excluded
Pre-diagnostic depression vs. Post-diagnostic depression
 The study subjects were divided into two subgroups on the basis of depression onset
before or after the PD diagnosis.
 The codes for pre-diagnostic depression were extracted in the years before diagnosis of
PD; patients with pre- and post-diagnostic depression were observed until death or
December 2011
 Outcomes

 The primary clinical outcome was mortality.

 Other associated prognostic factors were accidental injury, dementia, and
aspiration pneumonia
 The secondary clinical outcome was levodopa equivalent dosage (LED) of all
anti-parkinsonian drugs at the end of every year after diagnosis of PD and
antidepressant use.
 Antidepressants were classified into 4 groups according to their proposed
mechanisms : tricyclic antidepressants (TCA), selective serotonin reuptake
inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), and other
antidepressants.
 Statistics

 Stata version 111 (College Station, TX, USA) was used to perform all
statistical analyses.
 t test and Pearson chi-squared test were used to compare age,
distribution of gender, and confounders (hypertension, DM,
hyperlipidemia, and IHD) between the two groups ofPD patients.
Results

Baseline cohort
characteristics
Results
Hazard ratios of outcome variables associated with onset of
depression
Results
Levodopa equivalent dosage (LED) and cumulative equivalent dosage of
antidepressants in each group
 Discussion

 Two main findings were seen in the current study:

1) PD patients with post-diagnostic depression were associated with
significantly higher risks of dementia and were also older at the time of
PD diagnosis than PD patients with pre-diagnostic depression
2) mortality, accidental injury, motor condition and severity of depression
revealed no significant difference between PD patients with pre-
diagnostic and post-diagnostic depression
 Cognitive deficits may occur as a form of global cognitive decline or as an
impairment of specific cognitive domains in depressed PD patients.
 In our study, PD patients with post-diagnostic depression had a
significantly higher occurrence of dementia. This could possibly be
explained by different spreading routes and older age.
 Increasing age is a major risk factor for the development of dementia in PD
patients; thus the time for dementia development decreases with
increasing age at the onset of PD
 The proposed concept (based on nonmotor subtypes in PD) comprised the
brainstem route, the olfactory-limbic route, and the neocortical route.
Characteristics of the brainstem route were late-onset hyposmia, sleep-
dominant phenotype (including excessive daytime sleep and rapid eye
movement sleep behavior disorder), and dysautonomia (adrenergic problem,
gastrointestinal tract, and genitourinary symptoms). The brainstem route was
determined through Braak staging of Lewy pathology
 The olfactory-limbic route was characterized by early-onset anosmia and a
limbic phenotype (which is depressiondominant, fatigue-dominant, pain-
dominant, and weight-loss dominant).
 The neocortical route was characterized by older age of onset and cognitive-
dominant phenotypes (dementia, amnestic mild cognitive impairment, and falls
with cognitive impairment and apathy).
Our results :
 PD patients with pre-diagnostic depression and those with post-diagnostic
depression appeared to be involved in different developmental routes, which tend
to result in different phenotypes.
 The pathology of pre-diagnostic depression was involved in the caudal raphe
nuclei of the brainstem route (Stage II)
 Post-diagnostic depression appeared to involve the cortical area of the
neocortical route.
 PD patients with post-diagnostic depression, a significantly higher occurrence of
dementia may be explained by early involvement in the neocortical area.
 The present study may suggest that the different developmental routes of
pathology resulted in different phenotypes and clinical outcomes.
Thank you